Until today, cancer is one of the leading causes of deaths in the United States, even though progress has been made in reducing incidence and mortality rates and improving survival (see Jemal et al. 2010, CA Cancer J Clin. September-October 60(5):277-300). Further progress can be accelerated by improving diagnostic methods and means due to the fact that cancer development is often associated with the lack of specific recognition of tumor cells by the immune system.
Targeted cancer therapy comprises medication which interferes with specific targeted molecules (e.g., monoclonal or polyclonal antibodies) to directly block the growth of cancer cell. Thus, targeted cancer therapy may be more effective than traditional therapeutic approaches (e.g., resection, radiation, chemotherapy) and may be less harmful to normal cells. Monoclonal antibodies (mAb) can be designed to specifically bind to an extracellular domain or to a cell surface target of the target cell to stimulate the immune system of the patient. Monoclonal antibodies can also be created for numerous serious diseases (e.g., inflammatory diseases or different types of cancers). Thus, monoclonal antibodies may provide reliable and efficient therapeutic and diagnostic methods and means to e.g., detect early developmental stages of these diseases or to offer therapeutic approaches.
Natural killer cells (NK cells) constitute a major component of the innate immune system shaping the inflammatory and adaptive immune response (see Vivier et al. 2008, Nat. Immuno. 9:503-510) and playing a crucial role in the rejection of transformed and virally infected cells (see Smyth et al. 2002, Nat. Rev. Cancer 2:850-861; Lanier 2005, Annu Rev. Immunol. 23:225-274). NK cells survey target cells for expression of major histocompatibility complex (MHC) class I (see Parham 2005, Nat. Rev. Immunol. 5:201-204) which protects the target cell from NK cell activation and from NK cell attack. Target cells which lack MHC class I are directly killed by NK cells due to the induction of apoptosis (programmed cell death). The discovery of NK-activating receptors (e.g., the natural cytotoxicity receptor (NCR) family like NKp30) revealed that also activation signals are necessary for the activation of NK cells and tumor cell lysis (see Pende et al. 1999, Cancer Res. 62:6178-6186; Moretta et al. 2001, Annu Rev. Immunol. 19:197-223).
Recently, it could be shown that the human NKp30 directly interacts with the B7 family member B7-H6 whose expression on tumor cells induces NKp30-dependent cell activation and cytotoxity (see Brandt et al. 2009, J. Exp. Med. 206(7):1495-1503; US 2011/0081346). Hereby, the extracellular domain of NKp30 directly interacts with the extracellular domain of B7-H6 which is exclusively expressed on the surface of several tumor cell lines (see Brandt et al. 2009, J. Exp. Med. 206(7):1495-1503).